Chromatin Organization and Remodeling of Interstitial Telomeric Sites During Meiosis in the Mongolian Gerbil (Meriones unguiculatus)

Abstract

Telomeric DNA repeats are key features of chromosomes that allow the maintenance of integrity and stability in the telomeres. However, interstitial telomere sites (ITSs) can also be found along the chromosomes, especially near the centromere, where they may appear following chromosomal rearrangements like Robertsonian translocations. There is no defined role for ITSs, but they are linked to DNA damage-prone sites. We were interested in studying the structural organization of ITSs during meiosis, a kind of cell division in which programmed DNA damage events and noticeable chromatin reorganizations occur. Here we describe the presence of highly amplified ITSs in the pericentromeric region of Mongolian gerbil (Meriones unguiculatus) chromosomes. During meiosis, ITSs show a different chromatin conformation than DNA repeats at telomeres, appearing more extended and accumulating heterochromatin markers. Interestingly, ITSs also recruit the telomeric proteins RAP1 and TRF1, but in a stage-dependent manner, appearing mainly at late prophase I stages. We did not find a specific accumulation of DNA repair factors to the ITSs, such as gH2AX or RAD51 at these stages, but we could detect the presence of MLH1, a marker for reciprocal recombination. However, contrary to previous reports, we did not find a specific accumulation of crossovers at ITSs. Intriguingly, some centromeric regions of metacentric chromosomes may bind the nuclear envelope through the association to SUN1 protein, a feature usually performed by telomeres. Therefore, ITSs present a particular and dynamic chromatin configuration in meiosis, which could be involved in maintaining their genetic stability, but they additionally retain some features of distal telomeres, provided by their capability to associate to telomere-binding proteins.

Runaway GC Evolution in Gerbil Genomes

“…This may explain how approximately half of the weak-to-strong outliers in gerbils can map to subtelomeric regions in the M. musculus genome assembly yet not be outliers in this species. Nevertheless, high rates of karyotypic evolution have been documented in muroid rodents ( Ferguson-Smith and Trifonov 2007 ), with gerbil species differing in chromosome number relative to mice and carrying interstitial telomere sites, evidence of several large structural changes ( de la Fuente et al. 2014 ).…”

A chromosome-assigned Mongolian gerbil genome with sequenced centromeres provides evidence of a new chromosome

“…The only place that MsatC are found without interspersed copies of MsatA is on the X chromosome in what we term a 'C array'. While not interspersed with MsatC, there are a number of MsatA repeats that do appear at both ends of the X centromere (Figure 2D, for a high resolution image see Supplemental Material 3) and are detectable by FISH (de la Fuente et al 2014). The orientation of the Msat repeats is typically consistent across an array, however some arrays are composed of blocks of Msat repeats in alternating orientations with many copies of repeat in the forward orientation followed by many copies in the reverse orientation.…”

“…Karyotypically, it stains very dark and appears heterochromatic in G (Figure 3D) and C-banding images (Gamperl et al 1977;Gamperl and Vistorin 1980). It also displays delayed synapsis during the first meiotic prophase, when compared to all other chromosomes (de la Fuente et al 2007Fuente et al , 2014. On a technical level, it is the only chromosome that failed to assemble into a single chromosome-length scaffold (Figure 1), and even optical mapping was unable to improve the assembly.…”

“…In addition to these GC-skewed regions, gerbil genomes possess distinctive karyotypic features where one or more chromosomes with extensive regions of heterochromatin or that appear fully heterochromatic, showing as entirely dark in C-banding stains (Gamperl and Vistorin 1980) or coated by heterochromatin histone marks in immunofluorescence assays (de la Fuente et al 2014). Chromatin state is an important mechanism for the regulation of gene activity.…”

“…Chromosome 13 stains entirely dark in C-banding stains (Gamperl and Vistorin 1980) and is completely coated by heterochromatin histone marks in immunofluorescence assays (de la Fuente et al 2014). (Gamperl and Vistorin 1980) The genomes of the North African Gerbil (Gerbillus campestris), the hairy-footed gerbil (Gerbilliscus paeba), and the fat sandrat (Psammomys obesus) all contain a single heterochromatic chromosome (Solari and Ashley 1977;Gamperl and Vistorin 1980;Knight et al 2013).…”